Mercury-induced autoimmunity in Brown Norway rats: kinetics of changes in RT6+ T lymphocytes correlated with IgG isotypes of circulating autoantibodies to laminin 1

Kosuda, Linda L.; Whalen, Barbara J.; Greiner, Dale L.; Bigazzi, Pierluigi E.

doi:10.1016/s0300-483x(97)00180-7

Cited by 14 publications

(22 citation statements)

References 46 publications

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“…Given the present data, it is plausible to speculate that ART2 ϩ CD25 ϩ rat IENK cells could play a role in the processes that regulate both the "physiologic inflammation" that is characteristic of the gut generally (1) and the genetic predisposition to autoimmunity in the BB rat specifically. Consistent with this hypothesis, we have also documented the existence of relatively deficient IENK cell number and cytokine production in two unrelated rat strains, LEW and BN, which are also susceptible to autoimmunity (BN, susceptible to HgCl 2 -induced nephritis (38), and LEW, susceptible to experimental allergic encephalomyelitis (39)). These deficiencies were not observed in three strains, WF, F344, and DA, which have little or no predisposition to autoimmunity.…”

Section: Discussionsupporting

confidence: 76%

Deficiencies in Gut NK Cell Number and Function Precede Diabetes Onset in BB Rats

Todd

Forsberg

Greiner

et al. 2004

The Journal of Immunology

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Defects in the intestinal immune system may contribute to the pathogenesis of autoimmune diseases. Intraepithelial lymphocytes represent a substantial fraction of gut-associated lymphocytes, but their function in mucosal immunity is unclear. A newly described population of NK cells that spontaneously secrete IL-4 and IFN-γ is present in the intraepithelial lymphocyte compartment of the rat. We hypothesized that defects in the number or function of these cells would be present in rats susceptible to autoimmunity. We report that the number of NKR-P1A+CD3− intraepithelial NK (IENK) cells is deficient before onset of spontaneous autoimmune diabetes in diabetes-prone BB (BBDP) rats. The absolute number of recoverable IENK cells was only ∼8% of that observed in WF rats. Bone marrow transplantation from histocompatible WF donors reversed the IENK cell deficiency (and prevented diabetes) in these animals, suggesting a hemopoietic origin for their IENK cell defect. Analysis of diabetes-resistant BB rats, which develop autoimmune diabetes only after perturbation of the immune system, revealed IENK cell numbers intermediate between that of BBDP and WF rats. IENK cells were selectively depleted during treatment to induce diabetes. Prediabetic BBDP and diabetes-resistant BB animals also exhibited defective IENK cell function, including decreased NK cell cytotoxicity and reduced secretion of IL-4 and IFN-γ. IENK functional defects were also observed in LEW and BN rats, which are susceptible to induced autoimmunity, but not in WF, DA, or F344 rats, which are resistant. Defects in IENK cell number and function may contribute to the pathogenesis of autoimmune diseases including type 1 diabetes.

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Section: Discussionsupporting

confidence: 76%

Deficiencies in Gut NK Cell Number and Function Precede Diabetes Onset in BB Rats

Todd

Forsberg

Greiner

et al. 2004

The Journal of Immunology

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“…Total numbers of double-positive CD8+CD4+ thymocytes decrease, but total numbers of CD4+ single-positive thymocytes increase. We have also observed that HgC12-treated BN rats have a decrease of RT6+ T cells (202,210). Kinetic studies of this change have shown significant percentage decreases after 8, 1 1, and 15 days of HgCl2 treatment and an inverse correlation with autoimmune responses to laminin 1 (Figure 1).…”

Section: Mercury-induced Renal Autoimmunitymentioning

confidence: 54%

“…Kinetic studies of this change have shown significant percentage decreases after 8, 1 1, and 15 days of HgCl2 treatment and an inverse correlation with autoimmune responses to laminin 1 (Figure 1). Two-color flow cytometry has revealed that percentages of both RT6.2+CD4+ and RT6.2+CD8+ T lymphocytes decrease on day 15 of mercury treatment (202). Studies of diabetes-prone BB rats have suggested that RT6+ T cells may have a still unexplained immunoregulatory role (211)(212)(213)(214).…”

Section: Mercury-induced Renal Autoimmunitymentioning

confidence: 99%

Metals and Kidney Autoimmunity

Bigazzi¹

1999

Environmental Health Perspectives

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“…This includes increases in levels of anti-muscarine acetylcholine type-3 receptor IgG 1 autoantibody during Sjögren's syndrome (Gao et al, 2006). Another example is in autoimmune glomerulonephropathy wherein mercury exposure results in high serum levels of anti-lamin 1 IgG 1 autoantibody (Kosuda et al, 1998). Preferential production of anti-muscle-specific receptor kinase IgG 1 autoantibody has been observed in a model of Myasthenia gravis in mice (Ulusoy et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, IgG isotypes (against specific autoantigens) have been investigated for any potential contribution to the induction or relapse of certain autoimmune diseases (Bijl et al, 2002;Gao et al, 2006;Kosuda et al, 1998). Building on this, to investigate the T H 2-like immune profile in BTBR mice, in the study reported here, levels of IgG isotype (IgG 1 , IgG 2a , IgG 2b , IgG 3 ) in serum and whole brain or in homogenates of various brain regions (e.g.…”

Section: Introductionmentioning

confidence: 99%

Aberrant IgG isotype generation in mice with abnormal behaviors

Kim

et al. 2015

Journal of Immunotoxicology

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BTBR T+tf/J (BTBR) mice were recently cited as a suitable animal model for the study of autism because of their behavioral characteristics and immunological changes similar to those reported from autistic subjects. The BTBR mouse was reported to have significantly higher levels of serum IgG, brain IgG deposits and anti-brain IgG than highly social C57BL/6 mice, suggesting involvement of aberrant immune responses in the occurrence of autism. Upregulation of IgG production was investigated here, with a focus on the pattern of IgG isotype distribution compared with that in FVB/NJ (FVB) mice, another highly social control strain. The results indicated that levels of serum IgG 1 , IgG 2b and IgG 3 in post-natal day 21 BTBR mice was significantly higher than FVB mice, regardless of sex, resulting in higher IgG 1 :IgG 2a ratios in BTBR mice than in FVB mice (statistical significance in males). A similar outcome regarding the IgG 1 :IgG 2a ratio was observed in culture supernatants of bone marrow cells from these hosts. A presence of brain-reactive IgG in the sera of BTBR was higher than in FVB mice; levels of brainreactive IgG against whole brain homogenates were higher in BTBR than in FVB mice, with significant differences seen in the striatum and substantia nigra regions. Levels of IgG 1 deposited in the cerebellum, cortex, hippocampus or striatum of both BTBR male and female mice were significantly higher than in FVB counterparts. Overall, these results suggest that alterations in IgG isotype production or deposition in the brain could be implicated in the aberrant immune reactivities of BTBR mice.

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Mercury-induced autoimmunity in Brown Norway rats: kinetics of changes in RT6+ T lymphocytes correlated with IgG isotypes of circulating autoantibodies to laminin 1

Cited by 14 publications

References 46 publications

Deficiencies in Gut NK Cell Number and Function Precede Diabetes Onset in BB Rats

Deficiencies in Gut NK Cell Number and Function Precede Diabetes Onset in BB Rats

Metals and Kidney Autoimmunity

Aberrant IgG isotype generation in mice with abnormal behaviors

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